Christine A. Pratilas

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The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members. Using small-molecule inhibitors of MEK and an integrated genetic and pharmacologic analysis, we find that mutation of(More)
We present a novel method for deriving network models from molecular profiles of perturbed cellular systems. The network models aim to predict quantitative outcomes of combinatorial perturbations, such as drug pair treatments or multiple genetic alterations. Mathematically, we represent the system by a set of nodes, representing molecular concentrations or(More)
We present a powerful experimental-computational technology for inferring network models that predict the response of cells to perturbations, and that may be useful in the design of combinatorial therapy against cancer. The experiments are systematic series of perturbations of cancer cell lines by targeted drugs, singly or in combination. The response to(More)
Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models(More)
Drugs that inhibit the MAPK pathway have therapeutic benefit in melanoma, but responses vary between patients, for reasons that are still largely unknown. Here we aim at explaining this variability using pre- and post-MEK inhibition transcriptional profiles in a panel of melanoma cell lines. We found that most targets are context specific, under the(More)
Porto, the institutional repository of the Politecnico di Torino, is provided by the University Library and the IT-Services. The aim is to enable open access to all the world. Please share with us how this access benefits you. Your story matters. Abstract We present a powerful experimental-computational technology for inferring network models that predict(More)
Graphical Abstract Highlights d Most targets of MAPK pathway are regulated by it only in a subset of cell lines d Cell lines with high activity of IFN pathway are resistant to MEK inhibition d IFNa/b treatment enhances the cytotoxic response of MEK inhibition d In resistant cells, CytoC is released but caspases are not cleaved In Brief Litvin et al.(More)
Systematic prediction of cellular response to perturbations is a central challenge in biology, both for mechanistic explanations and for the design of effective therapeutic interventions. We addressed this challenge using a computational/experimental method, termed perturbation biology, which combines high-throughput (phospho)proteomic and phenotypic(More)
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